The objective of the proposed research are to contribute to the understanding and diagnosis of genetic human diseases by the development of a new technology based upon electrospray ionization mass spectrometry for rapid and accurate genotyping of single-nucleotide polymorphisms (SNPs) and short tandem repeats (STRs). Polymerase chain reaction (PCR) coupled with mass spectrometry is a near ideal platform for genotyping due to its high speed, accurate and precise mass measurements, and having the inherent ability to deduce primary structure via gas-phase sequencing. The proposed work will initially focus on elucidating the best strategy to prepare PCR products specifically for electrospray ionization mass spectrometry which is a formidable challenge. The precipitation or a more elaborate approach based on bio- affinity capture; both strategies can be automated in a 96-well format. Once a rapid preparation strategy is accomplished in the first 12-15 months of the proposed research, validation studies will be initiated gel- less, chip-less technology that is rapid, accurate and reliable for genotyping of SNPs and STRs which could realistically be placed in a clinical setting. Upon completion of the validation studies, unknown loci will be genotyped form the SNP panel of 90 to determine if there are any correlations between STR and SNP maps starting with the T-cell receptor beta loci located on chromosome 7. Concurrently, genes responsible for human deafness will be genotyped. All genotypes will be rapidly disseminated to the public through the development of a database including hyperlinks to other pertinent information regarding a specific polymorphic locus.